ROLE OF MRP–1 IN THE REGULATION OF STEROID RESPONSIVENESS IN UNCONTROLLED ASTHMA

Introduction: Inhaled Corticosteroids remain the mainstay therapy for asthma. Uncontrolled asthma (UA) dose not respond to the highest inhaled corticosteroids, which remains a challenge for clinicians. Multidrug resistance-associated protein 1 (MRP-1) are molecular “pumps,” which expel toxins and modulate corticosteroids’ pharmacokinetics and may lead to UA. Moreover, their role in UA is still not clear and needs further investigation. Our study evaluated the expression and functionality of MRP-1 in patients with controlled asthma (CA) and UA. Materials and Methods: UA was defined as a lack of control with high dose inhaled corticosteroids along with the use of other controller medications. Whole blood MRP-1 expression and functional activity on peripheral blood mononuclear cells (PBMCs) in UA (n=38), (mean age = 53.53 ± 11.85, male = 18) patients, CA) (n=60) (mean age = 51.65 ± 16.99, male = 31). MRP-1 was analyzed by flow cytometry. Result: Expression of MRP-1 positivity on lymphocyte gated population was significantly higher in UA than CA (p<0.001). Similarly, the functional activity of MRP-1 was significantly increased in UA as compared to CA (p<0.001). Receiver operating characteristic (ROC) curve analysis of UA was plotted to test the diagnostic accuracy of MRP-1expression; cut off percentage of MRP-1 was observed 11.21% with a sensitivity of 81.2% and specificity of 80%. Change in proximal forced expiratory volume tests (FEV1) showed a linear correlation with MRP-1. MRP-1 negatively correlated with FEV1 by Pearson correlation (p < 0.001), respectively. Conclusion: MRP-1 may help in the early diagnosis of poor response of corticosteroids. MRP-1 inhibitors may be used as an additional treatment for managing the poor response of corticosteroids.